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Jung et al. Soft Sci 2024;4:15 https://dx.doi.org/10.20517/ss.2024.02 Page 25 of 44

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with a power density of 3.5 mW/cm . During a 60-hour operation, the PPES monitored multiplexed signals
including metabolic analytes and the skin temperature. Moreover, with a CNTs-PDMS elastomer-based
strain sensor, on-body evaluation of the PPES was performed by measuring muscle contraction and
[249]
validated the promising use of human-machine interaction for the prosthetic control . In addition to
electrical sensing methods for measuring physical signals, acoustic sensing with ultrasonic transducers was
used to acquire more complex hemodynamic parameters. As shown in Figure 8E, a wearable device could
continuously and simultaneously monitor multiple biomarkers via enzymatic chemical sensors and physical
parameters, such as blood pressure and heart rate, via ultrasonic transducers. Glucose in ISF and lactate,
caffeine and alcohol in sweat were measured during the different daily activities. This multiple analysis
demonstrated that these skin-worn devices could ensure the understanding of various activities, such as
[250]
food or caffeine intake, digestion and exercise, and the forecasting of physiological changes .

Multi-electrochemical biomarkers
For more accurate analysis using a wearable non-invasive biosensor, Gao et al., from the group led by Javey,
showed the fully integrated biosensor array for in situ perspiration measurement, which is integrated with
functional components such as conditioning, processing and wireless transmission in the wristband
platform and measures sweat metabolites of glucose and lactate and electrolytes of potassium and sodium
[Figure 9A]. On-body perspiration analysis during cycling activity demonstrated real-time and selective
measurement of multi-electrolytes and metabolites of a human subject wearing a smart headband and a
smart wristband. In addition to flexible band-type configurations, various efforts have been made to develop
[34]
a form of wearable biosensor that can be easily integrated with existing accessories . As shown in
Figure 9B, Sempionatto et al., from the research group led by Wang, presented a fully integrated eyeglasses
platform for real-time monitoring of glucose, lactate and potassium in sweat. The screen-printed
electrochemical sensors were placed on the nose pads of eyeglasses, and a wireless electronic system was
[251]
attached on the arms of the eyeglasses frame . Efforts toward in-vivo sensing of multiplexed
electrochemical parameters involved developing needle-based microscale biosensor arrays [Figure 9C].
Active layers were electrodeposited on a polymeric polyimide substrate and integrated into the curved
surface of the medical needle. By measuring real-time glucose, lactate concentration, electrical conductivity
and pH, the needle-based biosensor array discriminated cancer from the normal tissues . For improving
[252]
the measurement accuracy of multiplexed glucose and lactate sensing, Yokus et al., from the group led by
Daniele, designed the wristwatch-shaped analog front-end of the electrochemical cells capable of measuring
twelve WE [Figure 9D]. Each WE collected chronoamperometric responses, and an accurate measurement
was obtained as an average of all collected data. This measurement strategy showed sensitivities of
-2
-1
-2
-1
-1
26.31 μA·cm ·mM for glucose, 1.49 μA·cm ·mM for lactate, 54 mV·pH for pH and 0.002 °C for
-1
temperature .
[253]
DKA is considered as a severe complication of both type 1 and type 2 DM and still has high rates of
mortality and morbidity . β-Hydroxybutyrate (β-HB) is well known as a key factor for the diagnosis of
[254]
DKA and a dominant biomarker of ketone formation. Because of this, many studies have been introduced
to fulfill the demands for self-testing of ketone [255,256] . Despite major improvements in DM management, a
real-time continuous ketone bodies monitoring (CKM) has not been as developed as CGM. Recently,
Teymourian et al., from the group led by Wang, presented a microneedle-based device that enables the
amperometric monitoring of HB and glucose, respectively [Figure 9E]. This CKM microneedle using HB
dehydrogenase (HBD) enzymatic reaction solved the major challenges associated with the reliable
confinement of the enzyme/cofactor couple (HBD/NAD ) and the fouling-free detection of nicotinamide
+
adenine dinucleotide (NADH). The potential feasibility of CKM microneedles was demonstrated by
showing an analytic performance, with good stability and high selectivity and sensitivity with a low